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Researchers discover why melanoma is so malignant

About 60,000 Americans will be diagnosed with melanoma this year, says the American Cancer Society, and 10,000 of those cases will be fatal. If not caught in the early stages, melanoma can be a particularly virulent form of cancer, spreading through the body with an efficiency that few tumors possess. Now, researchers at Whitehead Institute for Biomedical Research have discovered one of the reasons why this particular skin tumor is so ruthless. Unlike other cancers, melanoma is born with its metastatic engines fully revved.

"Other cancers need to learn how to spread, but not melanoma," says Whitehead Member Robert Weinberg, senior author of the paper that will be published September 4 in the early online edition of the journal Nature Genetics. "Now, for the first time, we understand the genetic mechanism responsible for this."

Metastasis (the spread of disease to an unconnected body part) is a highly inefficient, multi-step process that requires cancer cells to jump through many hoops. The cells first must invade a nearby tissue, then make their way into the blood or lymphatic vessels. Next they must migrate through the bloodstream to a distant site, exit the bloodstream, and establish new colonies. Researchers have wondered why melanoma in particular is able to do this not only more efficiently than other cancers, but at a far earlier stage. This new study shows that as melanocytes--cells that protect the skin from sun damage by producing pigmentation--morph into cancer cells, they immediately reawaken a dormant cellular process that lets them travel swiftly throughout the body.

Central to this reawakened process is a gene called Slug (named after the bizarre embryo shape that its mutated form can cause in fruit flies). Slug is active in the neural crest, an early embryonic cluster of cells that eventually gives rise to a variety of cell types in the adult, including dermal melanocytes. In this early embryonic stage, Slug enables the neu
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Source:Whitehead Institute for Biomedical Research


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